This proposal has 3 main objectives: a) To characterize genetically and biochemically a collection of heat-sensitive, nutritional and chloramphenicol-resistant mutants of Tetrahymena pyriformis isolated in my laboratory; b) To improve the efficiency with which recessive mutants of Tetrahymena can be isolated and; c) To attempt to demonstrate the occurrence of somatic recombination during vegetative propagation. The last objective will shed information on a parameter which is crucial to the interpretation of genetic experiments designed to investigate the molecular organization of the genetic material of the macronucleus. The first two objectives will greatly facilitate genetic work with Tetrahymena, and will make possible the use of the type of experimental approach which has been called genetic dissection to the study of many problems of the cell biology of this organism. The utility of being able to use Tetrahymena for genetic dissection goes beyond the study of Tetrahymena. There are few (if any) other animal cells which combine the facility for doing both genetics and biochemistry which Tetrahymena has. Consequently, this organism has the potential of becoming a model system for animal cells, by providing a versatile experimental system in which problems of general significance to cell biology can be readily approached at the molecular level. Given the universality of the molecular basis of many cellular mechanisms, the concepts and methods derived from this system should have applicability to many health-related problems, such as the biology of disease-causing eucaryotic organisms, developmental problems (cancer and aging, for example) and "molecular" diseases.